Eckstein, Markus, Wirtz, Ralph Markus, Gross-Weege, Matthias, Breyer, Johannes, Otto, Wolfgang, Stoehr, Robert, Sikic, Danijel, Keck, Bastian, Eidt, Sebastian, Burger, Maximilian, Bolenz, Christian, Nitschke, Katja, Porubsky, Stefan ORCID: 0000-0002-7647-7265, Hartmann, Arndt and Erben, Philipp ORCID: 0000-0002-8279-7636 (2018). mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants. Int. J. Mol. Sci., 19 (11). BASEL: MDPI. ISSN 1422-0067

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Abstract

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan (R)-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20(+)/KRT5(-), 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20(+)/KRT- tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Eckstein, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirtz, Ralph MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gross-Weege, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Breyer, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Otto, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoehr, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sikic, DanijelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keck, BastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eidt, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burger, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolenz, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitschke, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Porubsky, StefanUNSPECIFIEDorcid.org/0000-0002-7647-7265UNSPECIFIED
Hartmann, ArndtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erben, PhilippUNSPECIFIEDorcid.org/0000-0002-8279-7636UNSPECIFIED
URN: urn:nbn:de:hbz:38-167011
DOI: 10.3390/ijms19113396
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 19
Number: 11
Date: 2018
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COMPREHENSIVE MOLECULAR CHARACTERIZATION; BREAST-CANCER; CARCINOMA; IDENTIFICATION; VALIDATION; RECURRENCE; CYSTECTOMY; PORTRAITS; PREDICTOR; SUBTYPESMultiple languages
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16701

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